A Study of Mezagitamab in Adults With Primary Immunoglobulin A Nephropathy Receiving Stable Background Therapy

A Phase 1b, Multicenter, Open-Label Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Mezagitamab (TAK-079) in Patients With Primary IgA Nephropathy in Combination With Stable Background Therapy

This study will have two parts. The main aims are to:

• check the side effects from mezagitamab.
• check for long-term side effects from mezagitamab.

Before starting the study, participants will be asked to provide a 24-hour urine sample. A few weeks later, if enrolled they will begin receiving a subcutaneous injection (under the skin) of mezagitamab once a week for 8 weeks then once every 2 weeks for 16 weeks. When treatment has ended, there will be a 24-week follow-up period.

Participants who receive benefit from the treatment may continue in the second part of the study where they will be monitored for up to 96 weeks and possibly retreated for another 24 weeks.

Study Overview

• Status: Active, not recruiting
• Conditions: Glomerulonephritis; Kidney Disease
• Intervention / Treatment: Drug: Mezagitamab

Detailed Description

The drug being tested in this study is called mezagitamab. Mezagitamab is being tested for the first time in this patient population and might help to treat people who have Primary Immunoglobulin (IgA) Nephropathy. This study will evaluate the safety, tolerability, pharmacokinetics, and efficacy of mezagitamab in combination with stable background therapy.

The study will enroll approximately 16 participants. The study will consist of 2 key components: a main study and a long-term extension (LTE) study, which includes an observation period and a retreatment period. The observation period of the LTE study is a non-interventional study segment and the retreatment period of the LTE study consists of a redosing period in which participants will be administered mezagitamab at the same dose level as in the main study. Only participants who have a positive outcome during the main study will enter LTE study.

Participants will be enrolled to the following cohort:

• Mezagitamab

This multi-center trial will be conducted in the United States, Europe, and Asia Pacific. The overall time to participate in this study is approximately 154 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Takeda Contact; Phone Number: +1-877-825-3327; Email: medinfoUS@takeda.com

Study Locations

• Australia
  • Queensland
    • Milton, Queensland, Australia, 4064
      • Core Research Group
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health, Monash Medical Centre
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital,Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial Peoples Hospital
  • Shaanxi
    • Xian, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Csongrad
    • Szeged, Csongrad, Hungary, 6720
      • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
• Italy
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
• Japan
  • Aiti
    • Kasugai-Shi, Aiti, Japan, 486-0804
      • Kasugai Municipal Hospital
    • Toyoake-shi, Aiti, Japan, 470-1192
      • Fujita Health University Hospital
  • Hirosima
    • Hiroshima-shi, Hirosima, Japan, 734-8551
      • Hiroshima University Hospital
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-8604
      • Sapporo City General Hospital
• Korea, Republic of
  • Suwon-si, Korea, Republic of, 16499
    • Ajou University Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03080
      • Seoul National University Hospital
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital- Singapore
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron - PPDS
  • Barcelona, Spain, 8025
    • Fundacio Puigvert
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla
• Taiwan
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University Shuang Ho Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• United Kingdom
  • Hull, United Kingdom, HU3 2JZ
    • Hull Royal Infirmary
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE5 4PW
      • Leicester General Hospital
• United States
  • California
    • Northridge, California, United States, 91324
      • Amicis Research Center - Northridge - Nordhoff
  • Idaho
    • Nampa, Idaho, United States, 83687
      • Boise Kidney and Hypertension Institute - Frenova
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Renal biopsy report supporting diagnosis of primary IgAN or IgA vasculitis-associated nephritis within 10 years prior to the screening visit.
2. UPCR greater than or equal to (>=) 1 milligram per milligram (mg/mg) or urine protein excretion (UPE) >=1 gram per day (g/day) by 24-hour urine collection during the screening period.
3. Estimated glomerular filtration rate (eGFR) >=45 milliliter per minute per 1.73 square meter (mL/min/1.73m^2) at screening.
4. Receiving stable background therapy for IgAN (angiotensin-converting enzyme inhibitor [ACE-I] or angiotensin receptor blocker [ARB]) for 12 weeks prior to screening. The ACE-I and ARB dose should represent the maximum tolerated or maximum labeled dose, as determined by the investigator, for a minimum of 3 months and remain stable during the entire duration of the study.

Exclusion Criteria:

1. Kidney biopsy confirming significant renal disease other than IgAN.
2. Secondary IgAN (such as with significant liver disease, inflammatory bowel disease, and seronegative spondyloarthropathies).
3. Evidence of rapidly progressive glomerulonephritis (loss of >=50 percent (%) of eGFR within 3 months prior to the screening visit).
4. Diagnosis of nephrotic syndrome defined as 24-hour proteinuria greater than (>) 3.5 g/day, hypoalbuminemia (smaller than [<] 30 g/dL) with or without peripheral edema at the screening visit.
5. Diagnosis of acute active extrarenal IgA vasculitis (Henoch-Schönlein purpura) manifested by the involvement of other organs (palpable purpura, abdominal pain, and arthritis) at the screening visit and within 1 year prior to the screening visit.
6. Previous treatment with immunosuppressive agents such as cyclophosphamide, mycophenolate mofetil (MMF), cyclosporine, azathioprine, calcineurin inhibitors within 6 months prior to the screening visit or expected use of any of these agents for the duration of the study.

7. Use of systemic corticosteroids within 4 months from screening visit or expected use for the duration of the study.

   Use of B-cell-directed biologic therapies such as blisibimod, belimumab, rituximab, ocrelizumab or have used other biologics (example, anti-tumor necrosis factor [TNF], abatacept, anti-interleukin [IL]-6) within 6 months prior to the screening visit or expected use of any of these agents for the duration of the study.

8. Participation in another investigational study within 4 weeks or 5 half-lives of study drug, whichever is longer, before the screening visit (the 4-week window is derived from the date of the last study procedure, and/or AE related to the study procedure in the previous study, to the screening visit of the current study) or expected use of an investigational agent from another investigational study during the time of this study.
9. Administration of any vaccine within 28 days before the screening visit or of any live or live-attenuated vaccination planned for the duration of the study.
10. An opportunistic infection smaller than or equal to (<=) 12 weeks before screening visit or currently receiving treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria. A mild, localized herpes simplex infection within 12 weeks of study dosing is allowed, as long as the lesion has resolved prior to Day 1.
11. A positive T-cell interferon-gamma release assay (TIGRA) (result through QuantiFERON-TB Gold test or T-Spot/Elispot) at the screening visit.
12. A positive test result for hepatitis B surface antigen, or hepatitis B core antibody, or hepatitis C antibody, or HIV antibody/antigen at screening. However, an individual who has a known history of chronic hepatitis C and has been treated and fully cured of the disease, confirmed with a negative hepatitis C virus RNA polymerase chain reaction (PCR) test at screening, is not excluded on the basis of the positive hepatitis C antibody alone.
13. Inadequate organ and bone marrow function at screening visit.
14. Presence of uncontrolled or New York Heart Association (NYHA 1994) Class 3 or 4 congestive heart failure at the screening visit.
15. Uncontrolled diabetes manifested by glycosylated hemoglobin (HbA1c) >8% at the screening visit.
16. Current malignancy or history of malignancy during the previous 5 years, except adequately treated basal cell or squamous cell carcinomas of the skin or carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mezagitamab; Mezagitamab, subcutaneous injection, once weekly for 8 weeks then once every 2 weeks for 16 weeks in the Main Study. Same dosing regimen will be repeated in LTE Retreatment Period.	Drug: Mezagitamab; TAK-079 subcutaneous injection.; Other Names: TAK-079

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Main Study: Percentage of Participants With one or More Treatment-emergent Adverse Events (TEAEs), Grade 3 or Higher TEAEs, Serious Adverse Events (SAEs), and Adverse Events (AEs) Leading to Mezagitamab Discontinuation	The severity of TEAEs will be graded using National cancer institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.	Up to Week 48
LTE Observation Period: Percentage of Participants With one or More TEAEs, Grade 3 or Higher TEAEs and SAEs	The severity of TEAEs will be graded using NCI-CTCAE version 5.0.	Up to Week 96
LTE Retreatment Period: Percentage of Participants With one or More TEAEs, SAEs, Grade 3 or Higher TEAEs and AEs leading to Mezagitamab Discontinuation	The severity of TEAEs will be graded using NCI-CTCAE version 5.0.	Retreatment Week 0 to 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Main Study: Ctrough: Observed Serum Trough Concentrations of Mezagitamab		Week 0 Pre-dose and at multiple time points (up to Week 48)
Main Study: Serum IgA Levels		Week 0 Pre-dose and at multiple time points (up to Week 48)
Main Study: Percent Change From Baseline in Proteinuria Based on Urine Protein to Creatinine Ratio (UPCR)	UPCR is calculated by dividing the concentration of protein (milligram per deciliter [mg/dL]) in urine by the urine creatinine concentration (mg/dL).	Week 36
Main Study: Percentage of Participants Based on Antidrug Antibody (ADA) Levels in Serum	Percentage of participants in each category of the immunogenicity status (ADA-negative, ADA-positive and titer) will be determined in this study.	Up to Week 48
LTE Observation Period: Serum IgA Levels		Week 56 Pre-dose and at multiple time points (up to Week 96)
LTE Observation Period: Percent Change From Baseline in Proteinuria Based on UPCR	UPCR is calculated by dividing the concentration of protein (mg/dL) in urine by the urine creatinine concentration (mg/dL).	Up to Week 96
LTE Observation Period: Percentage of Participants Based on ADA Levels in Serum		Up to Week 96
LTE Retreatment Period: Percentage of Participants Based on ADA Levels in Serum	Percentage of participants in each category of the immunogenicity status (ADA-negative, ADA-positive and titer) will be determined in this study.	Up to Retreatment Week 48

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2022
• Primary Completion (Estimated): March 23, 2026
• Study Completion (Estimated): March 23, 2026

Study Registration Dates

• First Submitted: December 14, 2021
• First Submitted That Met QC Criteria: December 14, 2021
• First Posted (Actual): December 30, 2021

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Urologic Diseases; Nephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis
• Other Study ID Numbers: TAK-079-1006; 2021-005023-20 (EudraCT Number); jRCT2011220009 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes